Membranes

1
Membranes
2
Learning Objectives
Describe saturated and unsaturated fatty acids
note the naturally occuring cis isomer and the
absence of conjugated double bonds in unsaturated
fatty acids. Describe with structures the effect
of cis double bonds on the three-dimensional
configuration of fatty acids, and comment on the
effect this has in membranes.
Describe the physical properties of fatty acids.
Draw an example of a phospholipid
(phosphatidylcholine, phosphatidylethanolamine,
phosphatidylserine).
Draw an example of an ether-linked phospholipid
(plasmalogen or platelet-activating factor).
3
Learning Objectives
Describe the basic structure of
sphingolipids. Describe the fluid mosaic model of
membranes. Define integral and peripheral
membrane protein. Describe and interpret
hydropathy plots. Describe the transmembrane
segments of glycophorin and bacteriorhodopsin. Des
cribe the preferred location of tyrosine,
tryptophan, and charged amino acid residues in
transmembrane proteins. Describe one genetic
disease resulting from the abnormal accumulation
of membrane lipids. Describe the membrane
bilayer.
4
Fatty acids are carboxylic acids with hydrocarbon
chains ranging from 4 to 36 carbons long (C6 to
C36). In some fatty acids, this chain is
saturated (no double bonds). In others, the chain
contains one or more double bonds (unsaturated).
Oleic acid 181 D9
Stearic acid 180
Saturated fatty acids adopt an extended
conformation. The cis double bond in oleic acid
does not permit rotation and introduces a rigid
bend in the hydrocarbon tail. All other bonds
are free to rotate.
5
The packing of fatty acids into stable aggregates
Fully saturated fatty acids in the extended form
pack into nearly crystalline arrays, stabilized
by many hydrophobic interactions. The presence
of one or more cis double bonds interferes with
this tight packing and results in less stable
aggregates.
6
The double bonds of polyunsaturated fatty acids
are almost never conjugated (alternating single
and double bonds), but are separated by a
methylene group (red)
CH CH CH2 CH CH
In nearly all naturally occurring fatty acids,
the double bonds are in the cis configuration
C C
H
H
7
Physical properties of fatty acids
The physical properties of free fatty acids
(unesterified fatty acids having a free carboxyl
group) are largely determined by the length and
degree of unsaturation of the hydrocarbon chain.
Fatty acids are poorly soluble in water. Any
free fatty acids in the blood are non-covalently
bound to serum albumin. Most fatty acids in the
blood are not free, but esterified to glycerol or
glycerol derivatives. Lacking the charged
carboxylate group, esterified fatty acids are
even less soluble in aqueous solutions.
Glycerol
8
Triacylglycerols are fatty acid esters of glycerol
When glycerol has two different fatty acids at
C-1 and C-3, C-2 is a chiral center.
9
In most eukaryotic cells, triacylglycerols form a
separate phase of microscopic, oily droplets in
the aqueous cytosol, serving as depots of
metabolic fuel.
In vertebrates, specialized cells called
adipocytes (fat cells) store large amounts of
triacylglycerols as fat droplets that nearly fill
the cell.
Cross section of four guinea pig adipocytes
10
(No Transcript)
11
Phospholipids
The backbone of phospholipids L-glycerol-3-phosph
ate (or D-glycerol-1-phosphate)
12
Glycerolphospholipids
Membrane lipids in which two fatty acids are
attached in ester-linkage to the first and second
carbon of glycerol the third carbon of glycerol
has a highly polar or charged group attached
through a phosphodiester linkage.
13
(No Transcript)
14
The distribution of fatty acids in
glycerolphospholipids is specific for different
organisms, and specific for different tissues of
the same organism. The biological significance
of the variation in fatty acids and head groups
is not yet understood.
In general, glycerolphospholipids contain a C10
or C18 saturated fatty acid at C-1, and a C18 to
C20 unsaturated fatty acid at C-2.
15
(No Transcript)
16
Phospholipids with ether-linked fatty acids
ether-linked alkene
plasmalogen
About half of the phospholipids in vertebrate
heart tissue are plasmalogens.
17
A typical membrane lipid of archaebacteria
a diphytanyl tetraether lipid
18
Sphingolipids
These lipids have a polar head group and two
non-polar tails but contain no glycerol.
Sphingolipids are composed of one molecule of the
long-chain amino alcohol sphingosine, one
molecule of a long-chain fatty acid, and a polar
head group that is joined by a glycosidic or
phosphodiester linkage.
19
(No Transcript)
20
Ceramide is the structural parent of all
sphingolipids
sphingomyelins neutral (uncharged)
glycosphingolipids gangliosides
21
Sphingomyelins contain phosphocholine or
phosphoethanolamine as polar head group. These
lipids are especially prominent in myelin, a
membranous sheath that surrounds and insulates
the axons of some neurons.
Glycosphingolipids located in the outer face of
plasma membranes head groups have one or more
sugars connected directly to C-1 of ceramide.
Cerebrosides have a single sugar linked to
ceramide galactose is characteristic of neural
tissue, glucose is characteristic of non-neural
tissue.
Gangliosides most complex sphingolipids have
oligosaccharides as head group which contain
sialic acid (N-acetylneuraminic acid) at the
termini. (GM series has one sialic acid GD
series, two)
22
(No Transcript)
23
The human blood groups O, A, and B are determined
in part by the oligosaccharide head groups of
these glycosphingolipids. The same three
oligosaccharides are also found attached to
certain blood proteins.
24
Sialic acid has a negative charge at pH 7.
The amounts and kinds of gangliosides in the
plasma membrane change dramatically with
embryonic development. Tumor formation induces
the synthesis of a new complement of
gangliosides. Very low concentrations of a
specific ganglioside induce differentiation of
cultured neuronal tumor cells.
25
Inherited Human Diseases Resulting from Abnormal
Accumulations of Membrane Lipids
The polar lipids of membranes undergo constant
metabolic turnover. The rate of synthesis is
normally counterbalanced by the rate of
breakdown. The breakdown of lipids is catalyzed
by hydrolytic enzymes in lysosomes, each enzyme
capable of hydrolyzing a specific bond. When
sphingolipid degradation is impaired by a defect
in one of these hydrolytic enzymes, partial
breakdown products accumulate in the tissues,
causing serious disease.
26
(No Transcript)
27
The symptoms of Tay-Sachs are progressive
retardation in development, paralysis, blindness,
and death by age of 3 or 4 years.
28
(No Transcript)
29
Erythrocyte stained with osmium tetroxide and
viewed with an electron microscope.
Viewed in cross-section, all cell membranes share
a characteristic trilaminar appearance. The
plasma membrane appears as a three
layered structure 50-80 Angstroms thick. The
image consists of two electron-dense regions
separated by a less dense central region.
30
Lipid composition of membranes (rat hepatocyte)
31
A lipid bilayer is the basic structural element
of membranes
32
Fluid mosaic model for membrane structure
Proteins and lipids are free to move laterally
movement from one face of the bilayer to the
other is restricted.
33
(No Transcript)
34
integral membrane protein proteins firmly bound
to a membrane by hydrophobic interactions as
distinct from peripheral proteins they are
removable only by agents that interfere with
hydrophobic interactions, such as detergents,
organic solvents, or denaturants. peripheral
membrane protein proteins that are loosely or
reversibly bound to a membrane by hydrogen bonds
or electrostatic forces generally water soluble
once released from the membrane peripheral
proteins may serve as regulators of
membrane-bound enzymes or may limit the mobility
of integral proteins by tethering them to
intracellular structures.
35
Glycophorin (erythrocyte)
The red hexagons represent an oligosaccharide
containing 2 sialic acid, galactose, and
galactosamine.
Carbohydrates are components of the NM blood
group.
36
Bacteriorhodopsin
A single polypeptide chain folds into seven
hydrophobic a helices, each of which traverses
the lipid bilayer roughly perpendicular to the
plane of the membrane.
37
Hydropathy plots
The relative polarity of each amino acid has been
determined experimentally by measuring the free
energy change accompanying the movement of the
amino acids side chain from a hydrophobic
solvent into water.
An amino acid sequence is scanned by using a
window of from 7 to 20 residues summing the
free energies of transfer to calculate a
hydropathy index for that window. The x-axis is
the residue number for the middle of the window
the y-axis is the hydropathy index for the window.
38
(No Transcript)
39
(No Transcript)
40
(No Transcript)
41
Tyrosine and tryptophan residues cluster at the
water-lipid interface
Residues of tyrosine (orange) and tryptophan
(red) are found predominantly where the nonpolar
region of acyl chains meets the polar head group
region. Charged residues (lys, arg, glu, asp)
are shown in blue they tend to be found in the
aqueous phase.
42
Membrane proteins with b-barrel structures